1. Healthy volunteers;
2. Age 18 - 45 years;
3. Predominantly right-handed
4. Normal or corrected-to-normal vision;
5. Normal uncorrected hearing;
6. Willingness and ability to give written informed consent and willingness and ability to understand the nature and content, to participate and to comply with the study requirements.

- Exclusion criteria

Diagnosis (or history of) psychiatric treatment (e.g., severe depression, anorexia nervosa, severe mood disorders, mania, schizophrenia or borderline personality disorder) / Diagnosis (or history of) neurological treatment / Diagnosis (or history of) endocrine treatment / Diagnosis (or history of) neuroendocrine treatment (e.g., phechromocytoma, hyperthyroidism, Cushing’s syndrome) / (History of) melanoma / Presence of prolactin-dependent tumors (e.g., pituitary prolactinoma or breast cancer) / (History of) requent autonomic failure (e.g., vasovagal reflex syncope) / (History of) clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, cardiovascular, metabolic, ocular or pulmonary disease/disorders / (History of) epilepsy in adulthood (i.e. no insult after 18 years of age, no current medication for epilepsy and no insult in the last five years) / (History of) drug dependence (opiate, LSD, (meth)amphetamine, cocaine, solvents, or barbiturate) or alcohol dependence / (History of) Raynaud’s syndrome / Hypersensitivity to sulpiride, methylphenidate, entacapone, or sulpiride / One first degree or two or more second degree family members with a history of sudden death or ventricular arrhythmia / Suicidality / History of prescribed medication within the last month prior to the start of the study. / History of ‘over the counter’ medication within the last two months (with exception of occasional use of paracetamol, acetylsalicylic acid, and ibuprofen). / Use of MAO inhibitor, anaesthetic, anti-depressant or anti psychotic drugs within the week prior to the start of the study. / Average use of psychotropic medication or recreational drugs weekly or more. / Cannabis use within 2 weeks prior to the start of the study, and periods of more than 3 months using weekly or more in the last 6 months / Use of psychotropic medication, or of recreational drugs over a period of 72 hours prior to the test sessions, and use of alcohol within the last 24 hours before each measurement. / Average use of more than 3 alcohol beverages daily. / Average use of psychotropic medication or recreational drugs weekly or more. / Habitual smoking, i.e., more than a pack of cigarettes per week a self-reported inability or unease to cease smoking for 24 hours to testing. / Regular use of corticosteroids. / Uncontrolled hypertension, defined as diastolic blood pressure at rest > 95 mmHg or systolic blood pressure at rest > 180 mmHg / Hypotension, defined as diastolic blood pressure < 50 mm Hg or systolic < 95 mm Hg or resting pulse rate < 45 beats/min / Diabetes / Abnormal hearing or (uncorrected) vision. / First degree family member with schizophrenia, bipolar disorder or major depressive disorder

- mec approval received

yes

- multicenter trial

no

- randomised

yes

- masking/blinding

Double

- control

Placebo

- group

Crossover

- Type

2 or more arms, randomized

- Studytype

intervention

- planned startdate

1-sep-2016

- planned closingdate

1-sep-2020

- Target number of participants

100

- Interventions

Participants will take part in an intake screening, and if included, they will complete a battery of computerized tests after administration of methylphenidate / sulpiride / placebo, in and outside an fMRI scanner, at three separate occasions. Participants will also take part in one F-DOPA PET scan session where entacapone and carbidopa will be administered prior to PET scanning. On the days preceding testing, subjects will have to adhere to some simple restrictions with respect to medication, alcohol and drug intake.

5 separate time points; 1 intake session, 3 session with drug and placebo condition, F-DOPA PET session. Total testing time: 2.5-6 hours per session, total about 25 hours per participant, at least 1 week in between sessions, with the aim to finish testing within 3 months per participant.